CAFs-Derived Exosomal miRNA-130a Confers Cisplatin Resistance of NSCLC Cells Through PUM2-Dependent Packaging

Tao Zhang,1 Ping Zhang,2 Hong-Xia Li3 1Department of Tuberculosis, Linyi People’s Hospital, Linyi, Shandong 276034, People’s Republic of China; 2Reproductive Medicine, Linyi People’s Hospital, Linyi, Shandong 276034, People’s Republic of China; 3Endoscopic Roo...

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Autores principales:	Zhang T, Zhang P, Li HX
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	chemoresistance non-small cell lung cancer cancer-associated fibroblasts exosome mirna-130a pumilio homolog 2 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b1f66b24f35d48e7b519b001bbb9392f
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spelling	oai:doaj.org-article:b1f66b24f35d48e7b519b001bbb9392f2021-12-02T14:18:08ZCAFs-Derived Exosomal miRNA-130a Confers Cisplatin Resistance of NSCLC Cells Through PUM2-Dependent Packaging1178-2013https://doaj.org/article/b1f66b24f35d48e7b519b001bbb9392f2021-01-01T00:00:00Zhttps://www.dovepress.com/cafs-derived-exosomal-mirna-130a-confers-cisplatin-resistance-of-nsclc-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Tao Zhang,1 Ping Zhang,2 Hong-Xia Li3 1Department of Tuberculosis, Linyi People’s Hospital, Linyi, Shandong 276034, People’s Republic of China; 2Reproductive Medicine, Linyi People’s Hospital, Linyi, Shandong 276034, People’s Republic of China; 3Endoscopic Room, Linyi Chest Hospital, Linyi, Shandong 276034, People’s Republic of ChinaCorrespondence: Hong-Xia LiEndoscopic Room, Linyi Chest Hospital, No. 233 Fenghuang Avenue, Hedong District, Linyi, Shandong 276034, People’s Republic of ChinaTel +86-13265485365Email lihongxia4678264@163.comPurpose: Chemoresistance is a significant barrier to the treatment and management of non-small cell lung cancer (NSCLC). Exosomes play an essential role in intercellular communication. Understanding the mechanism underlying the role of tumor stroma, especially cancer-associated fibroblasts (CAFs), during chemoresistance would significantly contribute to the clinical application of chemotherapy agents.Results: In this study, we demonstrated that NSCLC-derived CAFs were innately resistant to cisplatin treatment and CAFs-conditioned medium significantly promoted the survival rate of NSCLC cells after cisplatin treatment. Additionally, CAFs-derived exosomes were taken up by NSCLC cells. Moreover, exosomal miRNA-130a was transferred from CAFs to recipient NSCLC cells and knockdown of miRNA-130a reversed the effect of CAFs-derived exosomes during chemoresistance of NSCLC cells. Furthermore, pumilio homolog 2 (PUM2), a RNA-binding protein, mediated the packaging of miRNA-130a into exosomes. The overexpression and knockdown of PUM2 promoted and inhibited tumor growth of xenograft mice, respectively.Conclusion: Taken together, these results suggest that CAFs-derived exosomes confer cisplatin resistance of NSCLC cells through transferring miRNA-130a and that PUM2 is a critical factor for packaging miRNA-130a into exosomes. This study indicates that CAFs-derived exosomal miRNA-130a may be a potential therapeutic target for cisplatin resistance in NSCLC.Keywords: chemoresistance, non-small cell lung cancer, cancer-associated fibroblasts, exosome, miRNA-130a, pumilio homolog 2Zhang TZhang PLi HXDove Medical Pressarticlechemoresistancenon-small cell lung cancercancer-associated fibroblastsexosomemirna-130apumilio homolog 2Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 561-577 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chemoresistance non-small cell lung cancer cancer-associated fibroblasts exosome mirna-130a pumilio homolog 2 Medicine (General) R5-920
spellingShingle	chemoresistance non-small cell lung cancer cancer-associated fibroblasts exosome mirna-130a pumilio homolog 2 Medicine (General) R5-920 Zhang T Zhang P Li HX CAFs-Derived Exosomal miRNA-130a Confers Cisplatin Resistance of NSCLC Cells Through PUM2-Dependent Packaging
description	Tao Zhang,1 Ping Zhang,2 Hong-Xia Li3 1Department of Tuberculosis, Linyi People’s Hospital, Linyi, Shandong 276034, People’s Republic of China; 2Reproductive Medicine, Linyi People’s Hospital, Linyi, Shandong 276034, People’s Republic of China; 3Endoscopic Room, Linyi Chest Hospital, Linyi, Shandong 276034, People’s Republic of ChinaCorrespondence: Hong-Xia LiEndoscopic Room, Linyi Chest Hospital, No. 233 Fenghuang Avenue, Hedong District, Linyi, Shandong 276034, People’s Republic of ChinaTel +86-13265485365Email lihongxia4678264@163.comPurpose: Chemoresistance is a significant barrier to the treatment and management of non-small cell lung cancer (NSCLC). Exosomes play an essential role in intercellular communication. Understanding the mechanism underlying the role of tumor stroma, especially cancer-associated fibroblasts (CAFs), during chemoresistance would significantly contribute to the clinical application of chemotherapy agents.Results: In this study, we demonstrated that NSCLC-derived CAFs were innately resistant to cisplatin treatment and CAFs-conditioned medium significantly promoted the survival rate of NSCLC cells after cisplatin treatment. Additionally, CAFs-derived exosomes were taken up by NSCLC cells. Moreover, exosomal miRNA-130a was transferred from CAFs to recipient NSCLC cells and knockdown of miRNA-130a reversed the effect of CAFs-derived exosomes during chemoresistance of NSCLC cells. Furthermore, pumilio homolog 2 (PUM2), a RNA-binding protein, mediated the packaging of miRNA-130a into exosomes. The overexpression and knockdown of PUM2 promoted and inhibited tumor growth of xenograft mice, respectively.Conclusion: Taken together, these results suggest that CAFs-derived exosomes confer cisplatin resistance of NSCLC cells through transferring miRNA-130a and that PUM2 is a critical factor for packaging miRNA-130a into exosomes. This study indicates that CAFs-derived exosomal miRNA-130a may be a potential therapeutic target for cisplatin resistance in NSCLC.Keywords: chemoresistance, non-small cell lung cancer, cancer-associated fibroblasts, exosome, miRNA-130a, pumilio homolog 2
format	article
author	Zhang T Zhang P Li HX
author_facet	Zhang T Zhang P Li HX
author_sort	Zhang T
title	CAFs-Derived Exosomal miRNA-130a Confers Cisplatin Resistance of NSCLC Cells Through PUM2-Dependent Packaging
title_short	CAFs-Derived Exosomal miRNA-130a Confers Cisplatin Resistance of NSCLC Cells Through PUM2-Dependent Packaging
title_full	CAFs-Derived Exosomal miRNA-130a Confers Cisplatin Resistance of NSCLC Cells Through PUM2-Dependent Packaging
title_fullStr	CAFs-Derived Exosomal miRNA-130a Confers Cisplatin Resistance of NSCLC Cells Through PUM2-Dependent Packaging
title_full_unstemmed	CAFs-Derived Exosomal miRNA-130a Confers Cisplatin Resistance of NSCLC Cells Through PUM2-Dependent Packaging
title_sort	cafs-derived exosomal mirna-130a confers cisplatin resistance of nsclc cells through pum2-dependent packaging
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/b1f66b24f35d48e7b519b001bbb9392f
work_keys_str_mv	AT zhangt cafsderivedexosomalmirna130aconferscisplatinresistanceofnsclccellsthroughpum2dependentpackaging AT zhangp cafsderivedexosomalmirna130aconferscisplatinresistanceofnsclccellsthroughpum2dependentpackaging AT lihx cafsderivedexosomalmirna130aconferscisplatinresistanceofnsclccellsthroughpum2dependentpackaging
_version_	1718391627279499264

CAFs-Derived Exosomal miRNA-130a Confers Cisplatin Resistance of NSCLC Cells Through PUM2-Dependent Packaging

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